25% of cases are associated with calreticulin gene CALR exon 10 mutation
5-10% of cases are associated with MPL gene mutations
rarely it may be inherited “Primary Hereditary Thrombocytosis” due to germline mutations which are mostly autosomal dominant 1) in either:
the thrombopoietin gene (THPO)
the thrombopoietin receptor gene (MPL) - include MPL-P106L, MPL-S505N (this may increase thrombotic risk), and MPL-W515R, as well as the polymorphism MPL-K39N termed MPL Baltimore
JAK2 kinase (V617F) gene - not inherited itself as this is a somatic mutation, but some families have familial predisposition
prognosis is much better than for myelofibrosis with 10 yr survival rates > 90%, and 20 yr survival rates around 75% for JAK-2 or MPL mutations, and ~85% for CALR mutations
patients are at risk of:
thrombosis (risk is ~ double for JAK-2 patients compared with MPL or CALR, being ~20% over 10yrs and 30% over ~20yrs)3)
haemorrhage
throbbing and burning of the hands and feet due to the occlusion of small arterioles by platelets (erythromelalgia)
low dose aspirin is often advised to prevent thrombosis but there may be an increased risk of bleeding if aspirin is initiated while the platelet count is very high
those at risk of complications or with very high platelet count, if not pregnant or lactating, consider either:
hydroxyurea
interferon-α
anagrelide - lower risk of DVT than with hydroxyurea but higher risk of arterial thrombus, severe bleeding and transformation to myelofibrosis
in patients who have life-threatening complications, the platelet count can be reduced rapidly using platelet apheresis